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Poly(ADP‐ribose)polymerase‐1 (PARP) activation and diabetic neuropathic pain
Author(s) -
Ilnytska Olga,
Mashtalir Nazar,
Drel Viktor R.,
Pacher Pal,
Yorek Mark A.,
Obrosova Irina G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a777-d
Subject(s) - neuropathic pain , nitrotyrosine , diabetic neuropathy , hyperalgesia , allodynia , medicine , sciatic nerve , dorsal root ganglion , infraorbital nerve , streptozotocin , diabetes mellitus , parp inhibitor , oxidative stress , poly adp ribose polymerase , neuralgia , pharmacology , anesthesia , endocrinology , chemistry , nociception , nitric oxide , anatomy , nitric oxide synthase , receptor , polymerase , biochemistry , dorsum , gene
PARP activation is a fundamental mechanism in the pathogenesis of diabetic complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic neuropathic pain. The experiments were performed in control and streptozotocin (STZ)‐diabetic rats treated with the PARP inhibitor 1,5‐isoquinolinediol (ISO, 3 mg kg −1 d −1 , i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw withdrawal and tail flick tests), mechanical hyperalgesia (von Frey anesthesiometer / rigid filaments, Randall‐Sellito tests), tactile allodynia (flexible von Frey filaments) and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine (NT) and poly(ADP‐ribose) immunoreactivities in the sciatic nerve, increased superoxide formation (hydroxyethidine method) and nitrotyrosine (NT) immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses including thermal and mechanical hyperalgesia and tactile allodynia, and, to a lesser extent, exaggerated formalin flinching behavior. Poly(ADP‐ribose), but not NT, abundance in sciatic nerve, as well as superoxide and nitrotyrosine in vasa nervorum were markedly reduced by ISO therapy. Dorsal root ganglion apoptosis (TUNEL assay) was not detected in any of the groups. In conclusion, PARP activation contributes to diabetic neuropathic pain by mechanisms that may include oxidative stress, but not neuronal apoptosis.